Parkinson's disease (PD) is the second most common neurodegenerative disorder. While a number of symptomatic therapies have been developed, no treatment has been identified that halts or slows this progressive disorder. For a number of reasons, we believe that it is appropriate to conduct prospective clinical trials of one or more of the more promising agents to determine whether they offer benefit. The aim of this application is for UCSF to continue participation as a clinical center in a collaborative study of neuroprotective agents. NET-PD was designed to enroll patients in a series of pilot studies and clinical trials of new agents for the treatment of Parkinson's disease. The role of the clinical sies is to identify, screen, enroll, treat, and follow patients in these trials; to report data in a timly manner to the data coordinating center; and to report adverse effects among enrolled patients. Currently, NET-PD is conducting the LS-1 study, a multi-center, double-blind, phase III clinical trial designed to determine whether or not creatine is more effective than placebo in slowing the clinical decline in PD patients with early, treated PD. Enrollment began in 2007 and ended in May of 2010, with all patients on treatment and followed for a minimum of 5 years or up to 8 years, through May 2015. A supplemental futility trial was initiated in May 2011 and continues enrollment. The FS-ZONE trial is a randomized, double-blind placebo-controlled futility study evaluating pioglitazone for the prevention of Parkinson's disease progression. The subjects will be followed for 44 weeks.